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Imperatorin and β‐sitosterol have synergistic activities in alleviating collagen‐induced arthritis
Author(s) -
Guo Qingqing,
Li Li,
Zheng Kang,
Zheng Guang,
Shu Haiyang,
Shi Yingjie,
Lu Cheng,
Shu Jun,
Guan Daogang,
Lu Aiping,
He Xiaojuan
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3ma0320-440rr
Subject(s) - imperatorin , rheumatoid arthritis , pharmacology , arthritis , mechanism (biology) , drug , biology , medicine , immunology , chemistry , philosophy , high performance liquid chromatography , epistemology , chromatography
Rheumatoid arthritis (RA) is a chronic disease with complex molecular network of pathophysiology, single drug is usually not full satisfactory because it is almost impossible to target the whole molecular network of the disease. Drug combinations that act synergistically with each another is an effective strategy in RA therapy. In this study, we aimed to establish a new strategy to search effective synergized compounds from Chinese herbal medicine (CHM) used in RA. Based on multi‐information integrative approaches, imperatorin (IMP) and β‐sitosterol (STO) were predicted as the most effective pair for RA therapy. Further animal experiments demonstrated that IMP+STO treatment ameliorated arthritis severity of collagen‐induced arthritis (CIA) rats in a synergistic manner, whereas IMP or STO administration separately had no such effect. RNA sequencing and IPA analysis revealed that the synergistic mechanism of IMP+STO treatment was related to its regulatory effect on 5 canonical signaling pathways, which were not found when IMP or STO used alone. Moreover, LTA, CD83, and SREBF1 were 3 important targets for synergistic mechanism of IMP+STO treatment. The levels of these 3 genes were significantly up‐regulated in IMP+STO group compared to model group, whereas IMP or STO administration separately had no effect on them. In conclusion, this study found that IMP and STO were 2 synergistic compounds from the CHM in RA therapy, whose synergistic mechanism was closely related to regulate the levels of LTA, CD83, and SREBF1.